Project Summary In this proposal a course of research is proposed to design and implement high-density multimodal (electrical and optical) neural probes on stainless steel for robust, reliable and large-scale recording from thousands of neurons in large animal (primate) brains. The neocortex consists of millions of neurons that form circuits that mediate perception, motor control, memory, and behavior. To understand the neural basis of brain function and dysfunction, novel tools are required to record and stimulate neural activity across different areas of the brain with high spatiotemporal resolution. Studying the non-human primate (NHP) central nervous system will lead to a better understanding of brain function in humans and will enable designing new therapeutics as well as next- generation prosthetics for humans. While the design of high-density neural interfaces for rodents has been the subject of extensive recent research, the design and implementation of high-density implantable neural interfaces for single-unit distributed recording and stimulation in NHPs remains challenging, mainly because of the required long form-factor and the expected level of reliability. Therefore, the design concepts, material platform, and the fabrication techniques optimized for realizing neural probes for rodents cannot be directly translated to designing probes for NHPs. In this proposal, a high-density optoelectrode will be developed, for the first time, to record and manipulate neural activity across different areas of the brain in NHPs with high spatiotemporal resolution. The neural implant proposed here is a monolithic device comprised of two layers of electrical recording electrodes and integrated photonic waveguides, all implemented on a long stainless steel shank. The electrical layer contains up to 128 recording channels in a small footprint of a 250 m-wide shank. The optical layer consists of a high-density (up to 32) photonic waveguides made of Parylene C polymer, a widely used polymer for insulating neural probes. The use of Parylene C as a material to realize highly efficient, compact and flexible photonic waveguides is a novel feature of the proposed optoelectrodes. To ensure reliability and robustness, the optical and electrical layers are monolithically implemented on a micromachined stainless steel substrate, which is a biocompatible, mechanically robust, and chemically stable material, widely used in medical practice in the form of cannulae and tubes. However, it has never been used for microfabrication of miniaturized devices since micromachining stainless steel is not easily possible. The proposed optoelectrodes will be monolithically microfabricated on stainless steel using a novel micromachining process to realize ultracompact, long and robust neural probes that can be easily implanted without damaging the tissue significantly and remain stable in the brain. The outcome of this research will be scalable, minimally-invasive, high-density optoelectrodes that can be mass-produced and provided to a wide user base. The proposed instrument will revolutionize the ability to study brain function in NHPs.